Date: Sunday, June 2, 2019
Session Time: 4:30pm-6:00pm
Presentation Time: 4:30pm-4:42pm
Location: Ballroom B
*Purpose: Eculizumab is a recombinant humanized IgG monoclonal antibody that inhibits C5, thereby preventing the activation of C5a and formation of membrane attack complex C5b-C9. In renal transplant patients eculizumab has been used to treat or prevent antibody-mediated rejection and disorders associated with abnormal complement activation. One study (Herlitz et al, JASN 2012) showed that eculizumab may deposit in native kidneys in patients with C3 glomerulonephritis (C3GN) or dense deposit disease, with IgG kappa deposition resembling monoclonal immunoglobulin deposition disease (MIDD). Eculizumab deposition in renal transplants has not been systematically studied.
*Methods: We identified 50 renal transplant patients who received eculizumab for at least 4 weeks from June 2008 to June 2018. Eculizumab was used in these patients to prevent or treat acute antibody-mediated rejection or C3GN. To be included in this study, the patient must have had at least one renal biopsy during the eculizumab treatment or within a month of the last dose. Biopsies were evaluated by light microscopy, immunofluorescence (IF) and electron microscopy (EM).
*Results: 50 kidney transplant recipients (19 M, 31 F) met the inclusion criteria and had 391 allograft biopsies in total (including 49 implantation biopsies). 44 kidneys were from living donors and 6 from deceased donors. The mean follow-up time was 35 months (range 2 – 108). Among the 50 patients, we identified 5 (10%) with post-transplant glomerular IgG deposition. Only one patient (2%) showed glomerular changes resembling MIDD with IgG2, IgG4, and kappa staining, consistent with eculizumab deposition; both subsequent biopsies over 4 months from this allograft showed similar changes. The other biopsies with glomerular IgG deposits had diagnoses of: segmental membranous glomerulonephritis (n=1), recurrent lupus nephritis (n=1), recurrent proliferative GN with monoclonal IgG3 lambda deposits (n=1), and de novo mesangial proliferative immune complex GN, not otherwise specified (n=1). Interestingly, the single patient with eculizumab deposits had recurrent C3GN, whereas none of the other patients in this series had C3GN or DDD as the native disease.
*Conclusions: Only rare kidney transplants (<1% of biopsies) from eculizumab-treated patients show eculizumab deposits, and such deposits were found only in a patient with C3GN. Glomerular eculizumab deposition may be associated with abnormalities in the alternative complement pathway. Other glomerular diagnoses with IgG deposits are more common.
To cite this abstract in AMA style:WANG D, Nasr SH, Farris AB, Schinstock CA, Alexander MP, Cornell LD. Eculizumab Deposition in Renal Transplants [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/eculizumab-deposition-in-renal-transplants/. Accessed July 4, 2020.
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